Storage of analysis code and output

Experiment I

Comparison to baseline

We first test whether TUS at parameters used in prior research reduced MEP amplitude from baseline, and whether that is also the case for stimulation of a control region (active control) or administration of a sound alone (sound-sham). The relevant conditions here are: 500 ms of TUS/AC at 32.5 W/cm2 without a masking stimulus, sound-sham, and baseline (i.e., TMS-only)

Condition
Baseline
500ms_AC
500ms_TUS
500ms_Mask
##                       Estimate Std. Error       df   t value     Pr(>|t|)
## (Intercept)          1.1123650 0.11347671 11.00082  9.802584 9.014327e-07
## Condition500ms_AC   -0.1194853 0.05216414 11.01509 -2.290563 4.270491e-02
## Condition500ms_Mask -0.1437009 0.04522184 11.02462 -3.177688 8.774258e-03
## Condition500ms_TUS  -0.1398309 0.06269135 11.08148 -2.230465 4.731814e-02
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Condition |           0.48 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

Stimulus duration (direct comparison)

Now we test whether there is an effect of stimulus duration on MEP amplitude, which inherently also involves a direct comparison between on-target, active control, and sham conditions.

Procedure
TUS
AC
Sham
Stimulus Duration
short
long
## Type III Analysis of Variance Table with Satterthwaite's method
##                             Sum Sq Mean Sq NumDF  DenDF F value   Pr(>F)   
## procedure                  0.29978 0.14989     2 11.048  1.2998 0.311198   
## stimulusDuration           1.16168 1.16168     1 11.024 10.0741 0.008833 **
## procedure:stimulusDuration 0.14904 0.07452     2 11.009  0.6462 0.542784   
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter                  | Eta2 (partial) |       95% CI
## ----------------------------------------------------------
## procedure                  |           0.19 | [0.00, 1.00]
## stimulusDuration           |           0.48 | [0.10, 1.00]
## procedure:stimulusDuration |           0.11 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

Stimulation intensity (free-water)

Now we want to determine whether there is any difference in MEP amplitude between trials where stimulation was delivered at 32.5 W/cm2 (originally 10 W/cm2) and 65 W/cm2 (originally 20 W/cm2). These intensities were applied both to the hand area and the contralateral face area.

Procedure
TUS
AC
Stimulation Intensity (free-water)
low
high
## Type III Analysis of Variance Table with Satterthwaite's method
##                       Sum Sq  Mean Sq NumDF  DenDF F value Pr(>F)
## procedure           0.070792 0.070792     1 11.039  0.6868 0.4248
## intensity           0.082657 0.082657     1 11.110  0.8020 0.3895
## procedure:intensity 0.010329 0.010329     1 11.012  0.1002 0.7575
## # Effect Size for ANOVA (Type III)
## 
## Parameter           | Eta2 (partial) |       95% CI
## ---------------------------------------------------
## procedure           |           0.06 | [0.00, 1.00]
## intensity           |           0.07 | [0.00, 1.00]
## procedure:intensity |       9.02e-03 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

Simulated intensity (TO BE COMPLETED)

To investigate whether there is a dose-response relationship between the estimated intensity intracranially and modulation of motor cortical excitability, we test for a relationship between simulated intensity and change in MEP amplitude from baseline (and from active control and sham conditions)

Work in progress.

Masking

We want to determine whether audible differences between stimulation sites (i.e., left-hemispheric hand motor area and right-hemispheric face motor area) may confound our results, which would be illustrated by an interaction between procedure(TUS/AC) and masking (unmasked/masked)

Procedure
TUS
AC
Masking
unmasked
masked
## Type III Analysis of Variance Table with Satterthwaite's method
##                      Sum Sq   Mean Sq NumDF  DenDF F value Pr(>F)
## procedure         0.0163725 0.0163725     1 11.021  0.1535 0.7027
## masking           0.0011414 0.0011414     1 11.080  0.0107 0.9195
## procedure:masking 0.0001484 0.0001484     1 11.038  0.0014 0.9709
## # Effect Size for ANOVA (Type III)
## 
## Parameter         | Eta2 (partial) |       95% CI
## -------------------------------------------------
## procedure         |           0.01 | [0.00, 1.00]
## masking           |       9.65e-04 | [0.00, 1.00]
## procedure:masking |       1.26e-04 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

Preperatory learning

It is possible that expectation of the TMS pulse underlies the observed motor inhibition for 500 ms ultrasonic and auditory stimuli. In this scenario, we would expect that during the first block of 500 ms, participants will show a decrease in MEP amplitude throughout the block as they learn to predict TMS by the auditory stimulus. During this experiment, participants receive two different stimulus durations, in addition to the sound-sham condition having slightly altered timing (i.e., onset ~50 ms earlier). Therefore, it would also be reasonable to expect that in each subsequent block, a number of trials will be needed to re-adjust to the relevant stimulus duration. This number of trials needed would be much lower than the amount of trials needed for initial learning in block 1. Notably, this can be confounded with a 15 second rest period prior to each block, and the known phenomenon that the first TMS pulse typically evokes a higher amplitude MEP.


First longer stimulus duration block for each participant:

## [1] "For trial per block 1-20"
## Type III Analysis of Variance Table with Satterthwaite's method
##             Sum Sq Mean Sq NumDF DenDF F value Pr(>F)
## trialblock 0.20519 0.20519     1    11  2.2296 0.1635

## [1] "For trial per block 1-10"
## Type III Analysis of Variance Table with Satterthwaite's method
##             Sum Sq Mean Sq NumDF DenDF F value  Pr(>F)  
## trialblock 0.87989 0.87989     1    11  8.2959 0.01496 *
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

Subsequent longer stimulus duration blocks for each participant:

## [1] "Trial number per block:"

## Type III Analysis of Variance Table with Satterthwaite's method
##             Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
## trialblock 0.12656 0.12656     1 11.085  1.0743 0.3221

## [1] "Trial number in total:"

## Type III Analysis of Variance Table with Satterthwaite's method
##         Sum Sq  Mean Sq NumDF  DenDF F value Pr(>F)
## Trial 0.033639 0.033639     1 10.852  0.2905 0.6008

Experiment II

Comparison to baseline

As in Experiment I, we first test whether TUS at parameters used in prior research reduced MEP amplitude from baseline, and whether that is also the case for stimulation of a control region (active control) or administration of a sound alone (sound-sham). The relevant conditions here are: 500 ms of TUS/AC at 6.35 W/cm2 without a masking stimulus, sound-sham, and baseline (i.e., TMS-only). Here, we also include TUS administered with a masking stimulus a pre-registered.

Condition
Baseline
Sham
TUS_10W_M
AC_10W_NM
TUS_10W_NM
##                       Estimate Std. Error       df   t value     Pr(>|t|)
## (Intercept)          0.9443794 0.04668147 26.02677 20.230282 1.916112e-17
## ConditionAC_10W_NM  -0.2216959 0.03964922 26.10652 -5.591431 7.009302e-06
## ConditionSham       -0.2232467 0.04161195 26.01801 -5.364966 1.283150e-05
## ConditionTUS_10W_M  -0.2090008 0.04143463 26.15454 -5.044109 2.944288e-05
## ConditionTUS_10W_NM -0.1815641 0.03776016 26.24006 -4.808352 5.453072e-05
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Condition |           0.40 | [0.19, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

Stimulation intensity & masking (direct comparison)

For Experiment II we have a more balanced experimental design, making it possible to include both intensity and masking in a single model. Here, we address the following questions:
1. Is there a difference in MEP amplitude following on-target or active control stimulation? (direct comparison)
2. Is there a difference in MEP amplitude when higher free-water intensities are administered?
3. Do audible differences possibly underly observed effects (interactions with masking)

A three-way interaction between stimulation site (on-target/active control), intensity (6.35/19.05 W/cm2), and masking (unmasked/masked) is relevant. For example, if audible differences play a role, we would expect and interaction between stimulation site and masking. If intensity is related to motor inhibition, we would expect an interaction between stimulation site and intensity, where higher intensities only result in further MEP attenuation for on-target, but not active control stimulation. Intensity and masking may interact with eachother, because higher intensity stimulation is louder, and thus masking may be less efficacious.

Procedure
TUS
AC
Masking
unmasked
masked
Stimulation intensity (free-water)
low
high
## Type III Analysis of Variance Table with Satterthwaite's method
##                               Sum Sq  Mean Sq NumDF   DenDF F value Pr(>F)
## procedure                   0.128761 0.128761     1 168.139  1.7507 0.1876
## masking                     0.123504 0.123504     1  29.767  1.6792 0.2050
## intensity                   0.094950 0.094950     1  49.798  1.2910 0.2613
## procedure:masking           0.041057 0.041057     1 100.098  0.5582 0.4567
## procedure:intensity         0.150823 0.150823     1  36.456  2.0506 0.1607
## masking:intensity           0.004736 0.004736     1  60.863  0.0644 0.8005
## procedure:masking:intensity 0.177470 0.177470     1  73.620  2.4129 0.1246
## # Effect Size for ANOVA (Type III)
## 
## Parameter                   | Eta2 (partial) |       95% CI
## -----------------------------------------------------------
## procedure                   |           0.01 | [0.00, 1.00]
## masking                     |           0.05 | [0.00, 1.00]
## intensity                   |           0.03 | [0.00, 1.00]
## procedure:masking           |       5.55e-03 | [0.00, 1.00]
## procedure:intensity         |           0.05 | [0.00, 1.00]
## masking:intensity           |       1.06e-03 | [0.00, 1.00]
## procedure:masking:intensity |           0.03 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].
## Warning in term == terms: longer object length is not a multiple of shorter
## object length
## Warning in term == names: longer object length is not a multiple of shorter
## object length

Simulated intensity

We ran simulations of acoustic wave propagation and thermal rise to obtain estimates of realized dosage and improved estimates of safety indices. Below you can see the simulated intracranial values for spatial-peak pulse-average intensity (Isppa), thermal rise (\(\Delta\)\(^\circ\)C), and the mechanical index (MI). The values are provided separately for the two applied free-water intensities: 6.35 and 19.05 W/cm2

Simulated indices for lower free-water intensity
mean intensity SD intensity mean temperature rise SD temperature rise mean mechanical index SD mechanical index
1.788624 0.5256269 0.0558333 0.0359621 0.4731703 0.0704265
Simulated indices for higher free-water intensity
mean intensity SD intensity mean temperature rise SD temperature rise mean mechanical index SD mechanical index
5.36593 1.576897 0.2144444 0.097474 0.8195595 0.1219829
## [1] "Analyses for lower stimultion intensity"
## [1] "Change from baseline"
## 
## Call:
## lm(formula = p2p_sqrt_baseCor ~ simIntensity, data = cropData)
## 
## Residuals:
##     Min      1Q  Median      3Q     Max 
## -42.705  -7.866   1.177  13.830  33.776 
## 
## Coefficients:
##              Estimate Std. Error t value Pr(>|t|)   
## (Intercept)   -47.769     13.922  -3.431  0.00218 **
## simIntensity   14.862      7.404   2.007  0.05612 . 
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 19.47 on 24 degrees of freedom
## Multiple R-squared:  0.1437, Adjusted R-squared:  0.1081 
## F-statistic: 4.029 on 1 and 24 DF,  p-value: 0.05612

## [1] "Change from active control"
## 
## Call:
## lm(formula = p2p_sqrt_vsAC ~ simIntensity, data = cropData)
## 
## Residuals:
##      Min       1Q   Median       3Q      Max 
## -16.7505  -4.5988  -0.4563   5.7450  24.6293 
## 
## Coefficients:
##              Estimate Std. Error t value Pr(>|t|)
## (Intercept)   4.24061    6.23587   0.680    0.503
## simIntensity -0.04407    3.31652  -0.013    0.990
## 
## Residual standard error: 8.722 on 24 degrees of freedom
## Multiple R-squared:  7.357e-06,  Adjusted R-squared:  -0.04166 
## F-statistic: 0.0001766 on 1 and 24 DF,  p-value: 0.9895

## [1] "Change from sham"
## 
## Call:
## lm(formula = p2p_sqrt_vsSham ~ simIntensity, data = cropData)
## 
## Residuals:
##     Min      1Q  Median      3Q     Max 
## -18.640  -9.361   0.977   6.894  25.519 
## 
## Coefficients:
##              Estimate Std. Error t value Pr(>|t|)
## (Intercept)     7.853      8.068   0.973    0.340
## simIntensity   -2.374      4.291  -0.553    0.585
## 
## Residual standard error: 11.28 on 24 degrees of freedom
## Multiple R-squared:  0.01259,    Adjusted R-squared:  -0.02855 
## F-statistic: 0.306 on 1 and 24 DF,  p-value: 0.5852

## [1] "Analyses for lower stimultion intensity"
## [1] "Change from baseline"
## 
## Call:
## lm(formula = p2p_sqrt_baseCor ~ simIntensity, data = cropData)
## 
## Residuals:
##     Min      1Q  Median      3Q     Max 
## -46.518 -14.021   0.513  14.153  41.378 
## 
## Coefficients:
##              Estimate Std. Error t value Pr(>|t|)   
## (Intercept)   -46.363     15.781  -2.938  0.00719 **
## simIntensity    4.125      2.798   1.474  0.15340   
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Residual standard error: 22.07 on 24 degrees of freedom
## Multiple R-squared:  0.08304,    Adjusted R-squared:  0.04484 
## F-statistic: 2.174 on 1 and 24 DF,  p-value: 0.1534

## [1] "Change from active control"
## 
## Call:
## lm(formula = p2p_sqrt_vsAC ~ simIntensity, data = cropData)
## 
## Residuals:
##     Min      1Q  Median      3Q     Max 
## -24.906  -7.180   3.592   6.997  24.439 
## 
## Coefficients:
##              Estimate Std. Error t value Pr(>|t|)
## (Intercept)     3.805      8.350   0.456    0.653
## simIntensity   -1.106      1.480  -0.747    0.462
## 
## Residual standard error: 11.68 on 24 degrees of freedom
## Multiple R-squared:  0.02273,    Adjusted R-squared:  -0.01799 
## F-statistic: 0.5581 on 1 and 24 DF,  p-value: 0.4623

## [1] "Change from sham"
## 
## Call:
## lm(formula = p2p_sqrt_vsSham ~ simIntensity, data = cropData)
## 
## Residuals:
##     Min      1Q  Median      3Q     Max 
## -29.905  -6.605  -2.728   6.384  35.309 
## 
## Coefficients:
##              Estimate Std. Error t value Pr(>|t|)
## (Intercept)     9.071      9.558   0.949    0.352
## simIntensity   -1.867      1.694  -1.102    0.282
## 
## Residual standard error: 13.37 on 24 degrees of freedom
## Multiple R-squared:  0.04813,    Adjusted R-squared:  0.008472 
## F-statistic: 1.214 on 1 and 24 DF,  p-value: 0.2815

Blinding to TUS (direct comparison)

Here, we first determine whether masking ultrasonic stimulation effectively blinded participants to whether or not they were receiving TUS. In this analysis, we consider stimulation site (on-target versus active control), masking (unmasked/masked), and intensity, because higher intensities are associated with a louder auditory confound, and thus possibly less effective blinding

## Analysis of Deviance Table (Type II Wald chisquare tests)
## 
## Response: yes
##                               Chisq Df Pr(>Chisq)    
## procedure                    2.9336  1    0.08676 .  
## masking                     31.0702  1  2.489e-08 ***
## intensity                    4.2932  1    0.03827 *  
## procedure:masking            0.5072  1    0.47635    
## procedure:intensity          0.6782  1    0.41021    
## masking:intensity            0.2528  1    0.61514    
## procedure:masking:intensity  0.0177  1    0.89409    
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

Blinding to TUS (comparison to 50%)

Here, we assess whether discrimintation ability was significantly different from change (i.e., 50%) for each condition.

## [1] "AC_10W_M"
## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  participant_level$yes
## V = 113.5, p-value = 0.9567
## alternative hypothesis: true location is not equal to 0.5

## [1] "AC_10W_NM"
## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  participant_level$yes
## V = 190.5, p-value = 0.09578
## alternative hypothesis: true location is not equal to 0.5

## [1] "AC_30W_M"
## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  participant_level$yes
## V = 159.5, p-value = 0.5043
## alternative hypothesis: true location is not equal to 0.5

## [1] "AC_30W_NM"
## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  participant_level$yes
## V = 230.5, p-value = 0.003631
## alternative hypothesis: true location is not equal to 0.5

## [1] "Sham"
## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  participant_level$yes
## V = 146, p-value = 0.4437
## alternative hypothesis: true location is not equal to 0.5

## [1] "TUS_10W_M"
## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  participant_level$yes
## V = 125, p-value = 0.6914
## alternative hypothesis: true location is not equal to 0.5

## [1] "TUS_10W_NM"
## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  participant_level$yes
## V = 196, p-value = 0.1732
## alternative hypothesis: true location is not equal to 0.5

## [1] "TUS_30W_M"
## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  participant_level$yes
## V = 108, p-value = 0.8027
## alternative hypothesis: true location is not equal to 0.5

## [1] "TUS_30W_NM"
## 
##  Wilcoxon signed rank test with continuity correction
## 
## data:  participant_level$yes
## V = 186, p-value = 0.01132
## alternative hypothesis: true location is not equal to 0.5

Audible differences

It is possible that, while blinding is effective, audible differences beteween the two stimulation sites remain (i.e., between stimulation of the left-hemispheric hand area and right-hemispheric face area). To test this, participants were presented with pairs of TUS, either both over the same site, or one over each site. These pairs were presented at either 6.35 W/cm2 or 19.05 W/cm2.

## ANOVA Table (type III tests)
## 
##           Effect DFn DFd      F        p p<.05   ges
## 1           same   1  26 28.139 1.51e-05     * 0.177
## 2      intensity   1  26  1.379 2.51e-01       0.004
## 3 same:intensity   1  26  0.856 3.63e-01       0.005

Preperatory learning

Previous research has reported that the amplitude of MEPs is reduced when participants are aware when the TMS pulse will be administered. In the context of our experiments, participants would first need to learn the timing of TMS relative to the onset of TUS. In this scenario, we would expect MEP amplitude on trials with a 500 ms auditory stimulus to begin at amplitudes near baseline MEP amplitude, followed by a reduction in MEP amplitude as participants learn when to expect TMS, and finally more stabilization of MEP amplitude throughout the remainder of the experiment.

Indeed, we see that over the first 50 trials this pattern is observed. To determine whether there is a significant relationship between trial and reduction in MEP amplitude, we split the data into Trial 1-20, and Trial 21-250, to see whether there is a significant decrease of MEP amplitude across initial trials followed by a stabilization.

## [1] "First 20 trials"
## Type III Analysis of Variance Table with Satterthwaite's method
##       Sum Sq Mean Sq NumDF  DenDF F value    Pr(>F)    
## Trial 1.0276  1.0276     1 25.949  16.644 0.0003808 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

## [1] "Trial 20-250"
## Type III Analysis of Variance Table with Satterthwaite's method
##         Sum Sq  Mean Sq NumDF  DenDF F value Pr(>F)
## Trial 0.014894 0.014894     1 25.942  0.2107   0.65

Experiment III

Part 1

Comparison of sound-sham to baseline

In Part 1, participants underwent 5 conditions: baseline, 1 kHz 500 ms tone, 1 kHz 700 ms tone, 12 kHz 500 ms tone, 12 kHz 700 ms tone. Here, we first test whether each of these conditions significantly reduce MEP amplitude from baseline (i.e., TMS only)

Condition
Baseline
12kHz_long
12kHz_short
1kHz_long
1kHz_short
##                        Estimate Std. Error       df   t value     Pr(>|t|)
## (Intercept)           0.9989508 0.04819728 15.01644 20.726290 1.842565e-12
## Condition12kHz_long  -0.1536070 0.05847780 14.63887 -2.626757 1.934979e-02
## Condition12kHz_short -0.3044756 0.05559294 14.61212 -5.476875 6.999497e-05
## Condition1kHz_long   -0.2419641 0.06747553 14.79834 -3.585953 2.754279e-03
## Condition1kHz_short  -0.2378596 0.08308604 14.60383 -2.862811 1.210937e-02

Pitch and duration

Next, we directly compare the four different tones to determine whether pitch, duration, or both ultimately affect MEP amplitude.

Pitch
1 kHz
12 kHz
Duration
short
long
## Type III Analysis of Variance Table with Satterthwaite's method
##                     Sum Sq Mean Sq NumDF  DenDF F value  Pr(>F)  
## Duration           0.77552 0.77552     1 15.181  7.1159 0.01743 *
## Frequency          0.00265 0.00265     1 14.874  0.0243 0.87825  
## Duration:Frequency 0.24353 0.24353     1 14.881  2.2345 0.15586  
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter          | Eta2 (partial) |       95% CI
## --------------------------------------------------
## Duration           |           0.32 | [0.04, 1.00]
## Frequency          |       1.63e-03 | [0.00, 1.00]
## Duration:Frequency |           0.13 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

Part 2

Ultrasonic stimulation, pitch, and tone duration

In Part 2, the four auditory stimuli were presented again, this time both with and without TUS. Here, we look to see whether there is an effect of ultrasonic stimulation on MEP amplitude over and above presentation of a auditory stimulus alone. We further investigate whether this may be modulated by the tone and/or duration of the auditory stimulus.

Ultrasonic stimulation
20W
0W
Pitch
1 kHz
12 kHz
Duration
short
long
## Type III Analysis of Variance Table with Satterthwaite's method
##                               Sum Sq Mean Sq NumDF  DenDF F value  Pr(>F)  
## Procedure                    0.04949 0.04949     1 15.423  0.4205 0.52621  
## Frequency                    0.58098 0.58098     1 14.776  4.9370 0.04235 *
## Duration                     0.05173 0.05173     1 15.145  0.4396 0.51729  
## Procedure:Frequency          0.02155 0.02155     1 15.159  0.1831 0.67471  
## Procedure:Duration           0.49674 0.49674     1 15.077  4.2212 0.05768 .
## Frequency:Duration           0.04537 0.04537     1 14.754  0.3855 0.54414  
## Procedure:Frequency:Duration 0.11475 0.11475     1 17.610  0.9751 0.33679  
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter                    | Eta2 (partial) |       95% CI
## ------------------------------------------------------------
## Procedure                    |           0.03 | [0.00, 1.00]
## Frequency                    |           0.25 | [0.01, 1.00]
## Duration                     |           0.03 | [0.00, 1.00]
## Procedure:Frequency          |           0.01 | [0.00, 1.00]
## Procedure:Duration           |           0.22 | [0.00, 1.00]
## Frequency:Duration           |           0.03 | [0.00, 1.00]
## Procedure:Frequency:Duration |           0.05 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

TMS intensity required under different conditions

In Part 1, the TMS intensity (in %MSO) was set to evoke a 1 mV MEP during baseline (i.e., TMS-only). During Part 2, the TMS intensity was set to evoke a 1 mV MEP four different times, once during the presentation of each of the four auditory stimuli. If the required TMS intensity for a 1 mV MEP is higher, that would indicate that MEPs were being attenuated by the auditory stimuli (as indeed observed in Part 1).

## [1] "ANOVA and follow-up"
## ANOVA Table (type III tests)
## 
##      Effect DFn DFd      F        p p<.05   ges
## 1 Condition   4  60 11.805 3.88e-07     * 0.021
## 
##  Pairwise comparisons using paired t tests 
## 
## data:  MSOlong$MSO and MSOlong$Condition 
## 
##             12kHz_long 12kHz_short 1kHz_long 1kHz_short
## 12kHz_short 0.49731    -           -         -         
## 1kHz_long   0.47597    0.23900     -         -         
## 1kHz_short  0.68385    0.42190     0.68232   -         
## Baseline    0.00097    0.00188     0.00022   0.00032   
## 
## P value adjustment method: none
## [1] "Mixed model and follow-up"
##             1kHz_short 1kHz_long 12kHz_short 12kHz_long
## Baseline             0         0           0          0
## 1kHz_short           1         0           0          0
## 1kHz_long            0         1           0          0
## 12kHz_short          0         0           1          0
## 12kHz_long           0         0           0          1
##                      Estimate Std. Error       df   t value     Pr(>|t|)
## (Intercept)           73.6875  2.5557941 15.86455 28.831548 3.938893e-15
## Condition1kHz_short    3.7500  0.6729134 60.00000  5.572782 6.270343e-07
## Condition1kHz_long     3.9375  0.6729134 60.00000  5.851421 2.172582e-07
## Condition12kHz_short   3.2500  0.6729134 60.00000  4.829745 9.819370e-06
## Condition12kHz_long    3.5000  0.6729134 60.00000  5.201263 2.520368e-06
## Type III Analysis of Variance Table with Satterthwaite's method
##           Sum Sq Mean Sq NumDF DenDF F value    Pr(>F)    
## Condition 171.05  42.762     4    60  11.805 3.882e-07 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## $`emmeans of Condition`
##  Condition   emmean   SE   df lower.CL upper.CL
##  Baseline      73.7 2.56 15.9     68.3     79.1
##  1kHz_short    77.4 2.56 15.9     72.0     82.9
##  1kHz_long     77.6 2.56 15.9     72.2     83.0
##  12kHz_short   76.9 2.56 15.9     71.5     82.4
##  12kHz_long    77.2 2.56 15.9     71.8     82.6
## 
## Degrees-of-freedom method: kenward-roger 
## Confidence level used: 0.95 
## 
## $`pairwise differences of Condition`
##  1                        estimate    SE df t.ratio p.value
##  Baseline - 1kHz_short      -3.750 0.673 60  -5.573  <.0001
##  Baseline - 1kHz_long       -3.938 0.673 60  -5.851  <.0001
##  Baseline - 12kHz_short     -3.250 0.673 60  -4.830  <.0001
##  Baseline - 12kHz_long      -3.500 0.673 60  -5.201  <.0001
##  1kHz_short - 1kHz_long     -0.188 0.673 60  -0.279  0.7815
##  1kHz_short - 12kHz_short    0.500 0.673 60   0.743  0.4604
##  1kHz_short - 12kHz_long     0.250 0.673 60   0.372  0.7116
##  1kHz_long - 12kHz_short     0.688 0.673 60   1.022  0.3110
##  1kHz_long - 12kHz_long      0.438 0.673 60   0.650  0.5181
##  12kHz_short - 12kHz_long   -0.250 0.673 60  -0.372  0.7116
## 
## Degrees-of-freedom method: kenward-roger
Values
Condition SE MSO
Baseline 2.763933 73.6875
1kHz_short 2.348703 77.4375
1kHz_long 2.534553 77.6250
12kHz_short 2.649636 76.9375
12kHz_long 2.461739 77.1875

 



To verify that the intensities are appropriate, the MEP amplitude should be approximately equal across all the four applied intensities.

MEP amplitudes at ~1 mV MSO
Condition SE p2p_sqrt
1kHz_short_0W 0.0678416 0.8914426
1kHz_long_0W 0.0720263 0.9032426
12kHz_short_0W 0.0683276 1.0047251
12kHz_long_0W 0.0602894 0.9288223
Baseline 0.0476694 0.9995522
Condition
## Type III Analysis of Variance Table with Satterthwaite's method
##            Sum Sq Mean Sq NumDF DenDF F value Pr(>F)
## Condition 0.60996 0.15249     4 14.94  1.2815 0.3211






While the MEP amplitudes do not significantly differ from each other, they do differ from one another up to 13%.
In Part I, there was a baseline condition. In Part 2, however, there was not. Nevertheless, we would like to know whether motor inhibition took place (as compared to baseline) for the conditions in Part 2. Therefore, we calculate the Adjusted MEP Amplitude. This measure will take into account not only the different TMS intensities applied, but also account for the differences in the TMS intensity’s ability to evoke a 1 mV MEP.
Below, you can see for each condition where TMS intensity was set to evoke a 1 mV amplitude, the factor required to actually have evoked exactly a 1 mV amplitude.
Condition
Condition ParticipantCode SE p2p_sqrt normalizeFactor
1kHz_short_0W S1 0.0780526 0.8470204 1.1806091
1kHz_short_0W S10 0.0634664 1.5055051 0.6642289
1kHz_short_0W S11 0.0594106 0.9000684 1.1110267
1kHz_short_0W S12 0.0587072 0.3242531 3.0840109
1kHz_short_0W S13 0.0921704 1.0257319 0.9749136
1kHz_short_0W S14 0.0323222 0.8044612 1.2430681
1kHz_short_0W S15 0.0965106 0.7300764 1.3697197
1kHz_short_0W S16 0.0623067 0.7633442 1.3100250
1kHz_short_0W S2 0.0648627 0.9620159 1.0394838
1kHz_short_0W S3 0.0722470 1.2341461 0.8102768
1kHz_short_0W S4 0.0855365 0.9796650 1.0207571
1kHz_short_0W S5 0.0621767 0.8960877 1.1159622
1kHz_short_0W S6 0.1073580 1.1672370 0.8567241
1kHz_short_0W S7 0.0638458 0.8201140 1.2193427
1kHz_short_0W S8 0.1281685 0.5832421 1.7145538
1kHz_short_0W S9 0.1051449 0.7201136 1.3886699
1kHz_long_0W S1 0.0594045 0.7053159 1.4178045
1kHz_long_0W S10 0.0773279 1.3568678 0.7369915
1kHz_long_0W S11 0.0728205 0.9197869 1.0872084
1kHz_long_0W S12 0.0668062 0.7086205 1.4111925
1kHz_long_0W S13 0.1454348 1.4254278 0.7015438
1kHz_long_0W S14 0.0776822 0.7340906 1.3622297
1kHz_long_0W S15 0.0824091 0.6660776 1.5013266
1kHz_long_0W S16 0.0397827 0.5778280 1.7306189
1kHz_long_0W S2 0.0602011 0.7079422 1.4125446
1kHz_long_0W S3 0.0730157 1.3576332 0.7365760
1kHz_long_0W S4 0.0705659 0.6064539 1.6489299
1kHz_long_0W S5 0.1030069 1.0107925 0.9893227
1kHz_long_0W S6 0.0802677 0.9777180 1.0227898
1kHz_long_0W S7 0.0593773 0.6292481 1.5891983
1kHz_long_0W S8 0.1453109 1.1744592 0.8514557
1kHz_long_0W S9 0.0871747 0.8936195 1.1190445
12kHz_short_0W S1 0.0661769 0.9456057 1.0575233
12kHz_short_0W S10 0.0771140 1.3270829 0.7535324
12kHz_short_0W S11 0.0722597 1.0749024 0.9303170
12kHz_short_0W S12 0.0813503 0.8454025 1.1828685
12kHz_short_0W S13 0.1283424 0.8183051 1.2220381
12kHz_short_0W S14 0.0707396 0.8684779 1.1514398
12kHz_short_0W S15 0.0961953 0.7102773 1.4079009
12kHz_short_0W S16 0.0502684 0.5256514 1.9024014
12kHz_short_0W S2 0.0830281 0.8648062 1.1563284
12kHz_short_0W S3 0.0837238 1.3731674 0.7282434
12kHz_short_0W S4 0.0954151 0.7778999 1.2855124
12kHz_short_0W S5 0.0868036 1.2888419 0.7758904
12kHz_short_0W S6 0.1262734 1.0697581 0.9347908
12kHz_short_0W S7 0.0981261 1.1125775 0.8988138
12kHz_short_0W S8 0.1029919 1.5546259 0.6432416
12kHz_short_0W S9 0.0842689 0.9182201 1.0890635
12kHz_long_0W S1 0.0736127 0.7510728 1.3314288
12kHz_long_0W S10 0.0688922 1.2703267 0.7871991
12kHz_long_0W S11 0.0441020 0.9313775 1.0736784
12kHz_long_0W S12 0.1055087 0.9458055 1.0572998
12kHz_long_0W S13 0.1372278 0.9032992 1.1070530
12kHz_long_0W S14 0.0836243 0.7973843 1.2541004
12kHz_long_0W S15 0.0439669 0.6359112 1.5725466
12kHz_long_0W S16 0.0361035 0.6587108 1.5181168
12kHz_long_0W S2 0.0602011 0.7079422 1.4125446
12kHz_long_0W S3 0.0569948 1.4871731 0.6724167
12kHz_long_0W S4 0.1176358 0.8119685 1.2315748
12kHz_long_0W S5 0.0881689 1.3171626 0.7592077
12kHz_long_0W S6 0.1587037 1.0126376 0.9875201
12kHz_long_0W S7 0.0723476 0.8519831 1.1737322
12kHz_long_0W S8 0.1610778 0.9443384 1.0589424
12kHz_long_0W S9 0.0847524 0.8340639 1.1989490
Baseline S1 0.0831449 1.0870603 0.9199122
Baseline S10 0.0641499 1.1361589 0.8801586
Baseline S11 0.1428946 1.2554183 0.7965473
Baseline S12 0.1016682 0.9854720 1.0147422
Baseline S13 0.1426936 1.1357613 0.8804667
Baseline S14 0.0641702 0.9014603 1.1093112
Baseline S15 0.0644333 0.6655947 1.5024158
Baseline S16 0.1319401 1.1845919 0.8441726
Baseline S2 0.0720395 0.8031923 1.2450319
Baseline S3 0.1006844 1.1022015 0.9072752
Baseline S4 0.0570554 0.7626954 1.3111394
Baseline S5 0.1099815 1.0686523 0.9357581
Baseline S6 0.1480828 1.1743366 0.8515446
Baseline S7 0.0810162 0.8716353 1.1472688
Baseline S8 0.1819932 1.1666718 0.8571391
Baseline S9 0.0977517 0.6919320 1.4452286





Now that the MEP amplitudes have been adjusted to on average 1 mV per applied intensity, we can correct MEP amplitudes for different applied intensities.

\[Adjusted~MEP = \sqrt{amplitude}_i * \frac{baseline~TMS~intensity_i}{applied~TMS~intensity_i}*\frac{realized~amplitude_{for~intended~1~mV} }{1}\]


This is how MEP amplitudes are transformed for the 5 conditions where TMS was intended to evoke a 1mV MEP:
MEP amplitudes at ~1 mV MSO
Condition SE p2p_sqrt
1kHz_short_0W 0 1
1kHz_long_0W 0 1
12kHz_short_0W 0 1
12kHz_long_0W 0 1
Baseline 0 1
Condition
## Type III Analysis of Variance Table with Satterthwaite's method
##               Sum Sq    Mean Sq NumDF DenDF F value Pr(>F)
## Condition 2.2382e-28 5.5955e-29     4  1162       0      1



Now a correction factor is applied to equalize the TMS intensities to baseline
MEP amplitudes at ~1 mV MSO
Condition SE p2p_sqrt
1kHz_short_0W 0.0110326 0.9491366
1kHz_long_0W 0.0104425 0.9477691
12kHz_short_0W 0.0110941 0.9571101
12kHz_long_0W 0.0112308 0.9527400
Baseline 0.0000000 1.0000000
Condition
## Type III Analysis of Variance Table with Satterthwaite's method
##            Sum Sq Mean Sq NumDF DenDF F value Pr(>F)
## Condition 0.45676 0.11419     4  1162  0.8907 0.4688




First, we test whether each condition in Part 2 reduces from baseline

##                 12kHz_long_0W 12kHz_long_20W 12kHz_short_0W 12kHz_short_20W
## Baseline                    0              0              0               0
## 12kHz_long_0W               1              0              0               0
## 12kHz_long_20W              0              1              0               0
## 12kHz_short_0W              0              0              1               0
## 12kHz_short_20W             0              0              0               1
## 1kHz_long_0W                0              0              0               0
## 1kHz_long_20W               0              0              0               0
## 1kHz_short_0W               0              0              0               0
## 1kHz_short_20W              0              0              0               0
##                 1kHz_long_0W 1kHz_long_20W 1kHz_short_0W 1kHz_short_20W
## Baseline                   0             0             0              0
## 12kHz_long_0W              0             0             0              0
## 12kHz_long_20W             0             0             0              0
## 12kHz_short_0W             0             0             0              0
## 12kHz_short_20W            0             0             0              0
## 1kHz_long_0W               1             0             0              0
## 1kHz_long_20W              0             1             0              0
## 1kHz_short_0W              0             0             1              0
## 1kHz_short_20W             0             0             0              1
##                             Estimate Std. Error       df    t value
## (Intercept)               0.99828001 0.04784225 15.03389 20.8660762
## Condition12kHz_long_0W   -0.11772795 0.04898765 15.67376 -2.4032169
## Condition12kHz_long_20W  -0.04941609 0.05242160 15.24092 -0.9426666
## Condition12kHz_short_0W  -0.03957859 0.05936217 15.01127 -0.6667308
## Condition12kHz_short_20W -0.11062596 0.06047875 14.93860 -1.8291709
## Condition1kHz_long_0W    -0.14194642 0.05665517 15.03911 -2.5054451
## Condition1kHz_long_20W   -0.13572020 0.06286661 15.09517 -2.1588598
## Condition1kHz_short_0W   -0.15277763 0.06774374 14.90185 -2.2552286
## Condition1kHz_short_20W  -0.21646148 0.07038850 14.79849 -3.0752392
##                              Pr(>|t|)
## (Intercept)              1.634993e-12
## Condition12kHz_long_0W   2.901591e-02
## Condition12kHz_long_20W  3.605553e-01
## Condition12kHz_short_0W  5.150620e-01
## Condition12kHz_short_20W 8.740488e-02
## Condition1kHz_long_0W    2.420917e-02
## Condition1kHz_long_20W   4.736167e-02
## Condition1kHz_short_0W   3.959608e-02
## Condition1kHz_short_20W  7.796576e-03
## $`emmeans of Condition`
##  Condition       emmean     SE   df lower.CL upper.CL
##  Baseline         0.998 0.0479 15.0    0.896    1.100
##  12kHz_long_0W    0.881 0.0528 15.0    0.768    0.993
##  12kHz_long_20W   0.949 0.0683 15.0    0.803    1.095
##  12kHz_short_0W   0.959 0.0649 15.0    0.820    1.097
##  12kHz_short_20W  0.888 0.0711 15.0    0.736    1.039
##  1kHz_long_0W     0.856 0.0683 15.0    0.711    1.002
##  1kHz_long_20W    0.863 0.0667 14.8    0.720    1.005
##  1kHz_short_0W    0.846 0.0657 15.0    0.706    0.985
##  1kHz_short_20W   0.782 0.0615 15.0    0.651    0.913
## 
## Degrees-of-freedom method: kenward-roger 
## Confidence level used: 0.95 
## 
## $`pairwise differences of Condition`
##  1                                estimate     SE   df t.ratio p.value
##  Baseline - 12kHz_long_0W          0.11773 0.0490 15.0   2.401  0.0298
##  Baseline - 12kHz_long_20W         0.04942 0.0525 15.0   0.942  0.3611
##  Baseline - 12kHz_short_0W         0.03958 0.0594 15.0   0.666  0.5153
##  Baseline - 12kHz_short_20W        0.11063 0.0605 15.0   1.828  0.0875
##  Baseline - 1kHz_long_0W           0.14195 0.0567 15.0   2.504  0.0243
##  Baseline - 1kHz_long_20W          0.13572 0.0638 14.8   2.129  0.0505
##  Baseline - 1kHz_short_0W          0.15278 0.0678 15.0   2.255  0.0395
##  Baseline - 1kHz_short_20W         0.21646 0.0704 15.0   3.074  0.0077
##  12kHz_long_0W - 12kHz_long_20W   -0.06831 0.0514 15.0  -1.328  0.2039
##  12kHz_long_0W - 12kHz_short_0W   -0.07815 0.0448 15.0  -1.745  0.1015
##  12kHz_long_0W - 12kHz_short_20W  -0.00710 0.0663 15.0  -0.107  0.9162
##  12kHz_long_0W - 1kHz_long_0W      0.02422 0.0463 15.0   0.523  0.6085
##  12kHz_long_0W - 1kHz_long_20W     0.01799 0.0507 14.5   0.355  0.7276
##  12kHz_long_0W - 1kHz_short_0W     0.03505 0.0619 15.0   0.566  0.5798
##  12kHz_long_0W - 1kHz_short_20W    0.09873 0.0651 15.0   1.517  0.1501
##  12kHz_long_20W - 12kHz_short_0W  -0.00984 0.0502 15.0  -0.196  0.8473
##  12kHz_long_20W - 12kHz_short_20W  0.06121 0.0521 15.0   1.175  0.2581
##  12kHz_long_20W - 1kHz_long_0W     0.09253 0.0459 15.0   2.015  0.0621
##  12kHz_long_20W - 1kHz_long_20W    0.08630 0.0594 14.7   1.453  0.1671
##  12kHz_long_20W - 1kHz_short_0W    0.10336 0.0620 15.0   1.668  0.1160
##  12kHz_long_20W - 1kHz_short_20W   0.16705 0.0754 15.0   2.216  0.0425
##  12kHz_short_0W - 12kHz_short_20W  0.07105 0.0587 15.0   1.210  0.2450
##  12kHz_short_0W - 1kHz_long_0W     0.10237 0.0566 15.0   1.808  0.0907
##  12kHz_short_0W - 1kHz_long_20W    0.09614 0.0524 14.6   1.834  0.0872
##  12kHz_short_0W - 1kHz_short_0W    0.11320 0.0778 15.0   1.455  0.1662
##  12kHz_short_0W - 1kHz_short_20W   0.17688 0.0787 15.0   2.249  0.0400
##  12kHz_short_20W - 1kHz_long_0W    0.03132 0.0595 15.0   0.526  0.6063
##  12kHz_short_20W - 1kHz_long_20W   0.02509 0.0650 14.8   0.386  0.7051
##  12kHz_short_20W - 1kHz_short_0W   0.04215 0.0774 15.0   0.545  0.5940
##  12kHz_short_20W - 1kHz_short_20W  0.10584 0.0738 15.0   1.435  0.1719
##  1kHz_long_0W - 1kHz_long_20W     -0.00623 0.0495 14.5  -0.126  0.9016
##  1kHz_long_0W - 1kHz_short_0W      0.01083 0.0641 15.0   0.169  0.8680
##  1kHz_long_0W - 1kHz_short_20W     0.07452 0.0753 15.0   0.989  0.3384
##  1kHz_long_20W - 1kHz_short_0W     0.01706 0.0713 14.9   0.239  0.8143
##  1kHz_long_20W - 1kHz_short_20W    0.08074 0.0764 14.9   1.057  0.3075
##  1kHz_short_0W - 1kHz_short_20W    0.06368 0.0482 15.0   1.321  0.2063
## 
## Degrees-of-freedom method: kenward-roger
## `summarise()` has grouped output by 'ParticipantCode'. You can override using
## the `.groups` argument.
## # A tibble: 143 × 6
## # Groups:   ParticipantCode [16]
##    ParticipantCode Condition       p2p_sqrt p2p_sqrt_MSOcor     SE AdjustedMEP
##    <chr>           <fct>              <dbl>           <dbl>  <dbl>       <dbl>
##  1 S1              Baseline           1.09            1.09  0.0765       1    
##  2 S1              12kHz_long_0W      0.751           0.716 0.0935       0.954
##  3 S1              12kHz_long_20W     1.11            1.06  0.0884       1.41 
##  4 S1              12kHz_short_0W     0.946           0.946 0.0700       1    
##  5 S1              12kHz_short_20W    0.913           0.913 0.121        0.965
##  6 S1              1kHz_long_0W       0.705           0.653 0.0779       0.925
##  7 S1              1kHz_long_20W      0.895           0.829 0.150        1.17 
##  8 S1              1kHz_short_0W      0.847           0.772 0.0840       0.912
##  9 S1              1kHz_short_20W     0.846           0.771 0.0727       0.910
## 10 S10             Baseline           1.14            1.14  0.0565       1    
## # … with 133 more rows
## [1] "For all comparisons but 1kHz_long_20W (because one missing)"
## 
##  Pairwise comparisons using paired t tests 
## 
## data:  cropData$p2p_sqrt_MSOcor and cropData$Condition 
## 
##                 Baseline 12kHz_long_0W 12kHz_long_20W 12kHz_short_0W
## 12kHz_long_0W   0.0273   -             -              -             
## 12kHz_long_20W  0.3420   0.2048        -              -             
## 12kHz_short_0W  0.5093   0.0984        0.8241         -             
## 12kHz_short_20W 0.0832   0.9198        0.2527         0.2349        
## 1kHz_long_0W    0.0227   0.5937        0.0593         0.0842        
## 1kHz_short_0W   0.0372   0.5720        0.1138         0.1618        
## 1kHz_short_20W  0.0076   0.1486        0.0449         0.0406        
##                 12kHz_short_20W 1kHz_long_0W 1kHz_short_0W
## 12kHz_long_0W   -               -            -            
## 12kHz_long_20W  -               -            -            
## 12kHz_short_0W  -               -            -            
## 12kHz_short_20W -               -            -            
## 1kHz_long_0W    0.5989          -            -            
## 1kHz_short_0W   0.5924          0.8713       -            
## 1kHz_short_20W  0.1749          0.3475       0.2106       
## 
## P value adjustment method: none
## [1] "For 1kHz_long_20S comparison"
## 
##  Paired t-test
## 
## data:  p2p_sqrt by Condition
## t = 1.3565, df = 14, p-value = 0.1964
## alternative hypothesis: true difference in means is not equal to 0
## 95 percent confidence interval:
##  -0.05656422  0.25124492
## sample estimates:
## mean of the differences 
##              0.09734035




Finally, we do pairwise comparisons between each auditory stimulus, with and without TUS.

## [1] "Direct comparison 1 kHz Short: sham versus TUS"
## 
##  Paired t-test
## 
## data:  p2p_sqrt by Condition
## t = 1.347, df = 15, p-value = 0.198
## alternative hypothesis: true difference in means is not equal to 0
## 95 percent confidence interval:
##  -0.0392928  0.1742229
## sample estimates:
## mean of the differences 
##              0.06746504
## [1] "Direct comparison 1 kHz Long: sham versus TUS"
## 
##  Paired t-test
## 
## data:  p2p_sqrt by Condition
## t = -0.10501, df = 14, p-value = 0.9179
## alternative hypothesis: true difference in means is not equal to 0
## 95 percent confidence interval:
##  -0.1161602  0.1053161
## sample estimates:
## mean of the differences 
##            -0.005422042
## [1] "Direct comparison 12 kHz Short: sham versus TUS"
## 
##  Paired t-test
## 
## data:  p2p_sqrt by Condition
## t = 1.2658, df = 15, p-value = 0.2249
## alternative hypothesis: true difference in means is not equal to 0
## 95 percent confidence interval:
##  -0.05283143  0.20734042
## sample estimates:
## mean of the differences 
##              0.07725449
## [1] "Direct comparison 12 kHz Long: sham versus TUS"
## 
##  Paired t-test
## 
## data:  p2p_sqrt by Condition
## t = -1.2931, df = 15, p-value = 0.2155
## alternative hypothesis: true difference in means is not equal to 0
## 95 percent confidence interval:
##  -0.18276462  0.04474396
## sample estimates:
## mean of the differences 
##             -0.06901033

Preperatory learning

Finally, like in Experiment I and II, we look into whether there is evidence for preperatory learning.

## [1] "For the first block with sound (regardless of duration)"

## Type III Analysis of Variance Table with Satterthwaite's method
##        Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
## Trial 0.10329 0.10329     1 14.718  1.3402 0.2654

## [1] "For the first block with 500 ms sound"

## Type III Analysis of Variance Table with Satterthwaite's method
##       Sum Sq Mean Sq NumDF DenDF F value Pr(>F)
## Trial 0.0192  0.0192     1 2.038  0.1745  0.716

## [1] "For the first block with 700 ms sound"

## Type III Analysis of Variance Table with Satterthwaite's method
##        Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
## Trial 0.10329 0.10329     1 14.718  1.3402 0.2654

## [1] "Trial number per block in subsequent blocks:"

## Type III Analysis of Variance Table with Satterthwaite's method
##             Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
## trialblock 0.16056 0.16056     1 14.602  1.2506 0.2815

## [1] "Trial number in total:"

## Type III Analysis of Variance Table with Satterthwaite's method
##        Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
## Trial 0.12648 0.12648     1 15.476  0.9788 0.3377

Experiment IV

Stimulation Intensity and Masking (two variants)

## [1] "For 3-level intensity:"
Intensity
low
medium
high
Masking
unmasked
masked
## Type III Analysis of Variance Table with Satterthwaite's method
##                    Sum Sq Mean Sq NumDF  DenDF F value    Pr(>F)    
## Masking           14.0884 14.0884     1 4053.1  70.815 < 2.2e-16 ***
## Intensity          8.3221  4.1611     2 4053.0  20.916 9.185e-10 ***
## Masking:Intensity  5.2178  2.6089     2 4053.0  13.114 2.105e-06 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter         | Eta2 (partial) |       95% CI
## -------------------------------------------------
## Masking           |           0.02 | [0.01, 1.00]
## Intensity         |           0.01 | [0.01, 1.00]
## Masking:Intensity |       6.43e-03 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "For 6-level intensity:"
Intensity
low
medium
high
Masking
unmasked
masked
## Type III Analysis of Variance Table with Satterthwaite's method
##                    Sum Sq Mean Sq NumDF  DenDF F value    Pr(>F)    
## Masking             54169   54169     1 4048.8 52.2984 5.673e-13 ***
## Intensity6          23593    4719     5 4048.2  4.5557 0.0003813 ***
## Masking:Intensity6   7602    1520     5 4048.4  1.4680 0.1968304    
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter          | Eta2 (partial) |       95% CI
## --------------------------------------------------
## Masking            |           0.01 | [0.01, 1.00]
## Intensity6         |       5.60e-03 | [0.00, 1.00]
## Masking:Intensity6 |       1.81e-03 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].




There is a significant interaction between masking and intensity. The analysis will not be split by masking.

## [1] "Testing the interaction for 3-level intensity:"
## [1] "Analysis of Intensity (for unmasked conditions"
Intensity
low
medium
high
## Type III Analysis of Variance Table with Satterthwaite's method
##           Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
## Intensity 4213.1  2106.5     2 1974.7  2.1724 0.1142
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Intensity |       2.20e-03 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Analysis of Intensity (for masked conditions"
Intensity
low
medium
high
## Type III Analysis of Variance Table with Satterthwaite's method
##           Sum Sq Mean Sq NumDF  DenDF F value  Pr(>F)  
## Intensity 6587.8  3293.9     2 2070.4  3.0298 0.04854 *
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Intensity |       2.92e-03 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

Comparison to baseline

For 3 level

## [1] "For 3-level intensity:"
## [1] "Baseline comparison for Audio_deep_30_3"
## Type III Analysis of Variance Table with Satterthwaite's method
##           Sum Sq Mean Sq NumDF  DenDF F value  Pr(>F)  
## Baseline 0.56591 0.56591     1 11.287   4.166 0.06534 .
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.27 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for NoAudio_deep_30_3"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF  DenDF F value    Pr(>F)    
## Baseline 4.2209  4.2209     1 10.692  26.812 0.0003339 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.71 | [0.40, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for Audio_deep_30_6"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF  DenDF F value   Pr(>F)   
## Baseline 2.1099  2.1099     1 11.168  11.283 0.006247 **
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.50 | [0.13, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for NoAudio_deep_30_6"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF  DenDF F value    Pr(>F)    
## Baseline 5.8219  5.8219     1 11.114  37.008 7.584e-05 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.77 | [0.50, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for Audio_deep_30_9"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF  DenDF F value  Pr(>F)   
## Baseline 2.4707  2.4707     1 11.224  13.389 0.00364 **
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.54 | [0.17, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for NoAudio_deep_30_9"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF DenDF F value    Pr(>F)    
## Baseline 2.9368  2.9368     1 11.03  21.155 0.0007602 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.66 | [0.31, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

For 6 level

## [1] "For 6-level intensity:"
## [1] "Baseline comparison for Audio_deep_30_2"
## Type III Analysis of Variance Table with Satterthwaite's method
##           Sum Sq Mean Sq NumDF  DenDF F value  Pr(>F)  
## Baseline 0.41531 0.41531     1 11.258  3.6073 0.08344 .
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.24 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for NoAudio_deep_30_2"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF  DenDF F value    Pr(>F)    
## Baseline 4.1215  4.1215     1 11.194  26.399 0.0003066 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.70 | [0.39, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for Audio_deep_30_3"
## Type III Analysis of Variance Table with Satterthwaite's method
##           Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
## Baseline 0.22797 0.22797     1 11.492  1.7812 0.2078
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.13 | [0.00, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for NoAudio_deep_30_3"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF  DenDF F value   Pr(>F)   
## Baseline 2.3108  2.3108     1 9.9238  19.013 0.001446 **
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.66 | [0.29, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for Audio_deep_30_5"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF DenDF F value  Pr(>F)  
## Baseline 1.2488  1.2488     1  11.1   7.849 0.01709 *
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.41 | [0.06, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for NoAudio_deep_30_5"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF  DenDF F value    Pr(>F)    
## Baseline 2.7739  2.7739     1 11.293  21.188 0.0007109 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.65 | [0.31, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for Audio_deep_30_6"
## Type III Analysis of Variance Table with Satterthwaite's method
##           Sum Sq Mean Sq NumDF  DenDF F value  Pr(>F)  
## Baseline 0.84875 0.84875     1 10.892   6.396 0.02821 *
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.37 | [0.03, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for NoAudio_deep_30_6"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF  DenDF F value   Pr(>F)   
## Baseline 1.5753  1.5753     1 9.9256  13.826 0.004038 **
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.58 | [0.19, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for Audio_deep_30_8"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF  DenDF F value   Pr(>F)   
## Baseline 1.6528  1.6528     1 11.184  11.913 0.005287 **
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.52 | [0.14, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for NoAudio_deep_30_8"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF  DenDF F value    Pr(>F)    
## Baseline 3.6029  3.6029     1 9.8513  27.009 0.0004231 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.73 | [0.41, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for Audio_deep_30_9"
## Type III Analysis of Variance Table with Satterthwaite's method
##           Sum Sq Mean Sq NumDF  DenDF F value  Pr(>F)  
## Baseline 0.92197 0.92197     1 11.319  6.4167 0.02729 *
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.36 | [0.03, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

## [1] "Baseline comparison for NoAudio_deep_30_9"
## Type III Analysis of Variance Table with Satterthwaite's method
##          Sum Sq Mean Sq NumDF  DenDF F value  Pr(>F)  
## Baseline  1.136   1.136     1 11.132  9.5289 0.01021 *
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## # Effect Size for ANOVA (Type III)
## 
## Parameter | Eta2 (partial) |       95% CI
## -----------------------------------------
## Baseline  |           0.46 | [0.09, 1.00]
## 
## - One-sided CIs: upper bound fixed at [1.00].

Preperatory learning

## [1] "For the first block with TUS (no masking)"

## Type III Analysis of Variance Table with Satterthwaite's method
##              Sum Sq  Mean Sq NumDF  DenDF F value Pr(>F)
## trialblock 0.014614 0.014614     1 11.526  0.1404 0.7147

## [1] "Trial number per block:"

## Type III Analysis of Variance Table with Satterthwaite's method
##            Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
## trialblock 0.2004  0.2004     1 11.252  1.1022 0.3158

## [1] "Trial number in total:"

## Type III Analysis of Variance Table with Satterthwaite's method
##        Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
## Trial 0.20027 0.20027     1 11.254   1.102 0.3159

Baseline corrected APB as dependent variable

## [1] "For the first block with TUS (no masking)"

## Type III Analysis of Variance Table with Satterthwaite's method
##            Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
## trialblock 787.02  787.02     1 11.211  1.0112 0.3358

## [1] "Trial number per block:"

## Type III Analysis of Variance Table with Satterthwaite's method
##            Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
## trialblock 317.72  317.72     1 10.962  0.3355 0.5741

## [1] "Trial number in total:"

## Type III Analysis of Variance Table with Satterthwaite's method
##       Sum Sq Mean Sq NumDF  DenDF F value Pr(>F)
## Trial 327.68  327.68     1 10.963   0.346 0.5683